Abstract

Background

Interleukin-1 beta converting enzyme (ICE, caspase 1) is a cysteine protease that
processes immature pro-IL-1β into active mature IL-1β. IL-1β is a pro-inflammatory
cytokine that mediates many of the physiological and behavioral responses to inflammation.
Genetic deletion of ICE has previously been shown to prevent some negative physiologic
responses to lipopolysaccharide (LPS)-induced inflammation.

Methods

Here we used a preclinical murine model to test the hypothesis that ICE is necessary
for development of depression-like behaviors following intracerebroventricular (ICV)
treatment with LPS. Adult male ICE knockout (ICE KO) and congenic wild-type C57BL/6
J (WT) mice were administered LPS either ICV at 100 ng/mouse or intraperitoneally
(IP) at 830 μg/kg body weight or an equal volume of saline as controls. Mice were
monitored up to 48 h after treatment for both sickness and depression-like behaviors.

Results

LPS given ICV induced a loss of body weight in both WT and ICE KO mice. This sickness
response was similar between WT and ICE KO mice. As expected, LPS administered ICV
increased immobility in the forced swim test (FST) and decreased sucrose preference
in WT mice but no change in either of these two depression-like behaviors was observed
in ICE KO mice. Expression of TNF-α and CD11b in brain was lower in ICE-KO mice at
24 h following ICV administration of LPS compared to WT mice. In contrast, when LPS
was given systemically, sickness response, depression-like behaviors, and expression
of these genes were similar between the two strains of mice.

Conclusions

These findings indicate that ICE plays a specific role in depression-like behavior
induced by a central inflammatory stimuli even though it is not required when LPS
is administered systemically.